Stimulation of the immune system, which includes stimulation of either or both innate immunity and adaptive immunity, is a complex phenomenon that can result in either protective or adverse physiologic outcomes for the host. In recent years there has been increased interest in the mechanisms underlying innate immunity, which is believed to initiate and support adaptive immunity. This interest has been fueled in part by the recent discovery of a family of highly conserved pattern recognition receptor proteins known as Toll-like receptors (TLRs) believed to be involved in innate immunity as receptors for pathogen-associated molecular patterns (PAMPs). Compositions and methods useful for modulating innate immunity are therefore of great interest, as they can affect therapeutic approaches to conditions involving autoimmunity, inflammation, allergy, asthma, graft rejection, graft versus host disease (GvHD), infection, cancer, and immunodeficiency, etc.
Recently there have been a number of reports describing the immunostimulatory effect of certain types of nucleic acid molecules, including CpG nucleic acids, GU rich ssRNA and double-stranded RNA. Of note, it has been reported that Toll-like receptor 9 (TLR9) recognizes bacterial DNA and oligonucleotides containing a CpG motif wherein the cytosine is unmethylated. See, e.g., Hemmi H et al. (2000) Nature 408:740-5; Bauer S. et al. (2001) Proc Natl Acad Sci USA 98:9237-42. The effects of CpG containing oligonucleotides on immune modulation have been described in U.S. patents such as U.S. Pat. Nos. 6,194,388; 6,207,646; 6,239,116; and 6,218,371; and published international patent applications, such as WO 98/37919, WO 98/40100, WO 98/52581, and WO 99/56755.
However, additional specific nucleic acid sequences capable of immunostimulatory action are desirable to provide immune stimulation in a variety of contexts. Therefore, what is needed are compositions and related methods that encompass such novel immunostimulatory nucleic acids.